Last reviewed · How we verify

NCT03692325

Safety and Efficacy of Nivolumab in Treating Oral Proliferative Verrucous Leukoplakia

Completed Phase 2 Results posted Last updated 1 October 2024
What this trial tests

Phase 2 trial testing Nivolumab in Leukoplakia, Oral in 33 participants. Completed in 30 August 2024.

Timeline
5 December 2018
Primary endpoint
1 September 2022
30 August 2024

Quick facts

Lead sponsorDana-Farber Cancer Institute
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposeprevention
Enrollment33
Start date5 December 2018
Primary completion1 September 2022
Estimated completion30 August 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, any sex, with Leukoplakia, Oral. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Best Overall Response Rate (BORR) Primary · Participants were followed up to 164 days.

BORR on treatment is the percentage of participants who achieved CR or PR. Best overall response is the best response recorded from study registration until the first disease progression/diagnosis of invasive OSCC (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Best overall response was determined by using composite scores based on both measurement and histology, matching to the response grid as following, (1)CR, a decrease of \>80% or more; (2)PR, a decrease of 40-80%; (3)SD, neither PR or PD, (4)PD, an increase of 10% or more.

GroupValue95% CI
Nivolumab36.420.4 – 54.9
COMD QLQ Score Change From Baseline to End of Treatment Secondary · Assessed at baseline and end of treatment. Treatment duration in days was a median (range) of 105 (21-164).

Quality of Life was evaluated using COMD QLQ (chronic oral mucosal diseases quality of life questionnaire). The range of the possible total score is 0-104, and low score is a good QoL.

GroupValue95% CI
Nivolumab-3-36 – 14
Grade 1/2 Toxicity Rate Secondary · Participants were followed up to 194 days.

The proportion of participants who experienced a maximum grade 1 or 2 adverse events regardless of treatment attribution based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.

GroupValue95% CI
Nivolumab0.750.58 – 0.89
Grade 3/4 Toxicity Rate Secondary · Participants were followed up to 194 days.

The proportion of participants who experienced a maximum grade 3 or 4 adverse events regardless of treatment attribution based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.

GroupValue95% CI
Nivolumab0.210.09 – 0.39
Time to the Next Surgery for a Head and Neck Malignancy Secondary · Participants were followed up to 13.3 months.

Time to Next Surgery is defined as time from the first study treatment to any head \& neck surgery or resection for biopsy-proven carcinoma in situ (CIS) or invasive oral carcinoma.

GroupValue95% CI
Nivolumab6.52.0 – 13.3
Cancer Free Survival at 2 Years (CFS2) Secondary · Participants were followed up to 2 years.

CFS2 is the probability of participants remaining alive and cancer-free at 2 years based on Kaplan-Meier methodology. Cancer-Free Survival (CFS) is defined as the time from study registration to development of invasive oral cancer or death due to any cause. Participants alive without disease progression or recurrence (of invasive oral cancer) are censored at date of last disease evaluation.

GroupValue95% CI
Nivolumab0.7280.526 – 0.855
2-year Overall Survival (OS) Rate Secondary · Participants were followed up to 2 years.

2-year OS rate was defined as the percentage of participants alive at 2 years.

GroupValue95% CI
Nivolumab10089.4 – 100
PD-L1 Combined Positive Scores (CPS) Secondary · PD-L1 CPS assessed at baseline.

PD-L1 CPS (programmed death-1 ligand 1 combined positive score) was calculated by dividing the number of PD-L1 staining cells by the total number of viable tumor cells and then multiplying by 100. Its range of possible values was 0-100, where higher scores were better when participants received PD-L1 targeted therapy.

GroupValue95% CI
Nivolumab100 – 80

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality was assessed up to 2 years; all adverse events were collected up to 194 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nivolumab
Serious: 6/33 (18%)
Deaths: 0/33

Serious adverse events (10 terms)

ReactionSystemNivolumab
HyperglycemiaMetabolism and nutrition disorders
Atrial fibrillationCardiac disorders
Atrial flutterCardiac disorders
Chest pain - cardiacCardiac disorders
Endocrine disorders - Other, specifyEndocrine disorders
Hepatitis viralInfections and infestations
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Blood bilirubin increasedInvestigations
Cardiac troponin T increasedInvestigations
Other adverse events (110 terms — click to expand)

ReactionSystemNivolumab
FatigueGeneral disorders
HypothyroidismEndocrine disorders
Oral painGastrointestinal disorders
HypertensionVascular disorders
Skin and subcutaneous tissue disorders - Other, specifySkin and subcutaneous tissue disorders
Aspartate aminotransferase increasedInvestigations
DiarrheaGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
HyperlipidemiaMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypophosphatemiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
Endocrine disorders - Other, specifyEndocrine disorders
NauseaGastrointestinal disorders
Gastroesophageal reflux diseaseGastrointestinal disorders
Gastrointestinal disorders - Other, specifyGastrointestinal disorders
ArthritisMusculoskeletal and connective tissue disorders
Sinus bradycardiaCardiac disorders
ConstipationGastrointestinal disorders
HyponatremiaMetabolism and nutrition disorders
EczemaSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Dry mouthGastrointestinal disorders
ThrushInfections and infestations
Pain in extremityMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
Chest pain - cardiacCardiac disorders
HyperthyroidismEndocrine disorders
Oral cavity fistulaGastrointestinal disorders
PainGeneral disorders
Creatinine increasedInvestigations
DizzinessNervous system disorders
DysgeusiaNervous system disorders
InsomniaPsychiatric disorders
Renal and urinary disorders - Other, specifyRenal and urinary disorders
Vaginal hemorrhageReproductive system and breast disorders

Most-reported serious reactions: Hyperglycemia, Atrial fibrillation, Atrial flutter, Chest pain - cardiac, Endocrine disorders - Other, specify, Hepatitis viral, Alanine aminotransferase increased, Aspartate aminotransferase increased.

Data from ClinicalTrials.gov NCT03692325 adverse events section.

Sponsor's own description

This research study is studying an immunotherapy drug, as a possible treatment for oral proliferative verrucous leukoplakia (OPVL).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches.
    Emran TB, Shahriar A, Mahmud AR, Rahman T, et al · · 2022 · cited 355× · PMID 35814435 · DOI 10.3389/fonc.2022.891652
  2. Tumor microenvironment and immunotherapy of oral cancer.
    Liu C, Wang M, Zhang H, Li C, et al · · 2022 · cited 78× · PMID 36209263 · DOI 10.1186/s40001-022-00835-4
  3. Nivolumab for Patients With High-Risk Oral Leukoplakia: A Nonrandomized Controlled Trial.
    Hanna GJ, Villa A, Nandi SP, Shi R, et al · · 2024 · cited 42× · PMID 37971722 · DOI 10.1001/jamaoncol.2023.4853
  4. Genetic Changes Driving Immunosuppressive Microenvironments in Oral Premalignancy.
    Rangel R, Pickering CR, Sikora AG, Spiotto MT. · · 2022 · cited 24× · PMID 35154165 · DOI 10.3389/fimmu.2022.840923
  5. Comprehensive Immunoprofiling of High-Risk Oral Proliferative and Localized Leukoplakia.
    Hanna GJ, Villa A, Mistry N, Jia Y, et al · · 2021 · cited 22× · PMID 36860910 · DOI 10.1158/2767-9764.crc-21-0060
  6. Advances and challenges in cancer immunoprevention and immune interception.
    Stanton SE, Castle PE, Finn OJ, Sei S, et al · · 2024 · cited 19× · PMID 38519057 · DOI 10.1136/jitc-2023-007815
  7. Advances in Nanotechnology for Cancer Immunoprevention and Immunotherapy: A Review.
    Koyande NP, Srivastava R, Padmakumar A, Rengan AK. · · 2022 · cited 18× · PMID 36298592 · DOI 10.3390/vaccines10101727
  8. Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis.
    Deng S, Wang S, Shi X, Zhou H. · · 2022 · cited 15× · PMID 36012205 · DOI 10.3390/ijms23168940

Verify or expand the search:

Other trials of Nivolumab

Trials testing the same drug.

Other Dana-Farber Cancer Institute trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03692325.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing